Prevention targets, novel therapies show promise for future of HF treatment

BOSTON — A presentation focusing on HF at the Cardiometabolic Health Congress examined where the field stands and where it is headed, covering epidemiology, prevention and new treatment options.

Clyde Yancy, MD, MSc, MACP, chief of cardiology at Northwestern University Feinberg School of Medicine, opened his talk by highlighting seemingly conflicting concepts.

“If you think about the messaging that we all have promulgated to the community, that over the last 2 to 3 decades we’ve seen a striking nearly 50% reduction in deaths due to CHD, it stands to reason … we should begin to see some evidence that the incidence of HF has been impacted by this.”

Clyde Yancy

With over a half million new cases per year, Yancy said the “disease du jour” would appear to be growing. However, he pointed to a recent study published in JAMA Internal Medicine that showed a 45% reduced incidence in HF with reduced ejection fraction (HFrEF) and a nearly 25% reduced incidence in HF with preserved ejection fraction (HFpEF).

“The burden is real and, as the population ages, we definitely see more disease,” he said. “But in terms of looking at the actual incidence rates, we’re beginning to see a bit of a change here that is in keeping with every other thing that we’ve seen in HF.”

Prevention is key

Yancy offered the audience a fresh perspective on prevention, noting that the conversation to-date has been limited due to inadequate data on approaches and populations.

Findings from an ongoing longitudinal cohort study involving four communities in the United States showed individuals with hypertension at enrollment had a 10-year incidence of HF that “far eclipsed” others, with African Americans showing the highest burden. According to Yancy, this presents a target population in which it’s possible to consider new approaches.

Yancy also discussed “provocative” insight that can be gleaned from a meta-analysis of more than 60 trials published in The Lancet, describing for the first time the risk for developing HF as a function of the aggregate burden of CV risk factors.

“As we go forward, we may be able to identify target populations like African Americans with hypertension, and target strategies like looking at a risk calculator, akin to what we do with lipid management, that might help us better discriminate in whom it is we should treat aggressively with antihypertensive therapy to avoid HF events,” he said. “This is a new dynamic that has not previously been embraced in the treatment of HF.”

Yancy reviewed the four stages of HF — at risk, asymptomatic disease, active symptoms, refractory disease — describing the progression as something that “does not afford the opportunity to go backwards” and “sets the template for how we approach disease.”

Treatment options

“We don’t yet have a compound that is uniquely indicated for HFpEF, but many of us believe that there may be drug therapies like corticoid antagonists that would be beneficial in that group,” Yancy said during the presentation.

Acknowledging the tendency for guidelines to be “unwieldly, too long and difficult,” Yancy shared a stepwise approach to treating HFrEF with algorithms.

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“All patients with [HFrEF], unless there is an overt contraindication, need RAAS blockade, an ACE inhibitor or angiotensin receptor blocker … and beta blocker,” he said. “Then, for the overloaded patient diuretics, for the African American patient [who is] persistently symptomatic, a combination of hydralazine-nitrates, and for the patient with reasonably intact renal function of all severities of HF, aldosterone antagonists.”

Yancy said this strategy affords clinicians the opportunity to choose the “right approach” from the available therapies.

But he went on to discuss novel treatments in HF, concentrating on two trials to illustrate ways to modify heart rate in addition to beta-blockers.

Yancy detailed “compelling” data when ivabradine (Corlanor, Amgen) was added to beta-blockers in the SHIFT study, with a 26% reduction in necessity for hospitalization, although there was no benefit on mortality. The drug was approved by the FDA in April 2015.

“The FDA has accepted these data in a way that is quite different than in the past,” he said, noting that the results were not generated in the United States. “The FDA has accepted these data as the basis for approval … without the benefit of a panel discussion, reflecting new dynamic in drug approval.”

The PARADIGM-HF dataset has become “famously important” in the past couple years, Yancy said. In a prototypical design that reflected previous studies in HF, the investigators explored a dual angiotensin receptor and neprilysin inhibition as an alternative to ACE inhibitor.

The researchers found “a profound benefit on CV mortality, a profound benefit on HF hospitalization, with P values almost unseen … [and] a profound benefit on reduction of total mortality, something we have hardly ever seen in a HF trial or even in all of CV clinical trials.”

Yancy cautioned it is important to put the positive results with sacubitril/valsartan in perspective, as most patients had mild to moderate HF and is likely not the approach for patients with advanced HF.

The FDA approved sacubitril/valsartan (Entresto, Novartis) in July 2015 for the reduction of CV death and HF-related hospitalization in patients with HFrEF.

In terms of guideline-directed therapy, Yancy questioned whether the field is prepared to include dual angiotensin receptor and neprilysin inhibition alongside RAAS inhibition, and also where ivabradine fits in the picture.

“We are configuring a guideline-writing committee as we speak and will begin deliberating this issue and hope to bring these things to print soon,” he said.

Promising outlook

In closing, Yancy said the future looks promising and listed some areas of research.

“We’re doing more studies with biomarkers now … [and] continuing to pursue regenerative therapies including gene transfer, stem cells and growth factors,” he said. “Clearly, we have to engage community if we want to make a bigger difference in this disease.” – by Allegra Tiver

Reference:

Yancy C. Prevention and Treatment of Heart Failure: Novel Therapies. Presented at: Cardiometabolic Health Congress; Oct. 21-24, 2015; Boston.

Disclosure: Yancy reports no relevant financial disclosures.